Intractable Diarrhea Due to Whipple's Disease in a Saudi: Report of a Case and Literature Review
1991; King Faisal Specialist Hospital and Research Centre; Volume: 11; Issue: 3 Linguagem: Inglês
10.5144/0256-4947.1991.343
ISSN0975-4466
Autores Tópico(s)Whipple's Disease and Interleukins
ResumoCase ReportsIntractable Diarrhea Due to Whipple's Disease in a Saudi: Report of a Case and Literature Review Dharmaraj H. Patil and MRCP(UK) Eric S. BoyeFRCPC Dharmaraj H. Patil Address reprint requests and correspondence to Dr. Patil: Department of Internal Medicine, King Fahad Hospital, P.O. Box 204, Al-Baha, Saudi Arabia. From the Department of Internal Medicine and Pathology, King Fahad Hospital, Al-Baha Search for more papers by this author and Eric S. Boye From the Department of Internal Medicine and Pathology, King Fahad Hospital, Al-Baha Search for more papers by this author Published Online:1 May 1991https://doi.org/10.5144/0256-4947.1991.343SectionsPDF ToolsAdd to favoritesDownload citationTrack citations ShareShare onFacebookTwitterLinked InRedditEmail AboutIntroductionWhipple's disease is a rare systemic disorder that can affect virtually any organ in the body. The small intestine is involved in the vast majority of patients. The disease has been reported most frequently in Caucasians but there have been a few cases reported in other races[1,2]. As far as we are aware, there have been no reports of Whipple's disease in Saudis. We report a case of Whipple's disease in a patient from the Al-Baha area located in southwestern Saudi Arabia.CASE REPORTA 50-year-old male Saudi farmer from Qunfudah on the Red Sea coast presented with a history of diarrhea of four years' duration. Prior to the onset of diarrhea he had been well and had undergone no form of abdominal surgery. He complained of passing three to five stools a day; these were pale, semisolid to watery in consistency and had an offensive odor. There was no history of rectal bleeding. He also complained of anorexia and occasional vomiting. Since the start of the diarrhea, he had gradually lost weight and become emaciated. In addition to the diarrhea and vomiting, he had vague abdominal discomfort but had not experienced severe abdominal pain at any time. He had been to several hospitals during the four years and had undergone several investigations, but according to him, no definite diagnosis had been made and he had not benefited from any of the treatments. Instead his condition had steadily worsened and he had been bedridden for about a month before being brought to this hospital.On examination the patient looked moribund. He was markedly cachectic, dehydrated, and pale. He had no significant lymphadenopathy and was afebrile. He had moderate bilateral leg edema. His blood pressure was 90/60 mm Hg with a pulse of 90/min. Respiratory, cardiovascular, and neurological findings were all normal. The abdomen was soft with no organomegaly, tenderness, or ascites. Bowel sounds were normal. Initial laboratory investigations revealed a low hemoglobin content (91 gm/L) and mean corpuscular volume (68.5 fL). His serum albumin (17 gm/L) and total protein (40 gm/L) levels were also low and serum calcium concentration (1.9 mmol/L) was in the low normal range. Apart from a positive stool for occult blood, all other laboratory investigations, including prothrombin time and stool microscopy and cultures, were normal. The Mantoux test was negative.His chest x-ray was normal but a plain x-ray of the abdomen showed a few gas-fluid levels with moderate dilatation of the small bowel. Upper abdominal ultrasound examination was normal. Barium meal and follow-through examination revealed slow'transit of barium through the small intestine. There was dilatation of loops of small bowel with flocculation of the barium. These changes are consistent with malabsorption syndrome. Abdominal computed tomographic scans showed no abnormality apart from dilated loops of small intestine. An echocardiogram was normal.Endoscopy revealed that the duodenal mucosal folds were edematous, friable, and covered with small yellowish waxy nodules. Endoscopic duodenal biopsies revealed a flat duodenal mucosa showing pronounced infiltration of the lamina propria by large mononuclear cells with abundant pale, foamy cytoplasm. There were also scattered clear spaces of variable sizes within the lamina propria (Figure 1). The foamy cells extended through the muscularis mucosae into the submucosa. They contained abundant periodic acid–Schiff (PAS)–positive granules that were resistant to diastase digestion (Figure 2). The PAS-positive granules were also free in the lamina propria. Sections stained by the Ziehl-Neelson technique did not reveal any acid-fast bacilli. These histological findings are characteristic of Whipple's disease. Rectal biopsies also showed the PAS-positive foamy cells within the rectal mucosa. A subsequent duodenal aspirate, stained by the PAS technique, revealed similar PAS-positive macrophages in the duodenal fluid. We are not aware that this last finding has been reported by other workers. However, PAS-positive macrophages have been found in the cerebrospinal fluid of patients with cerebral Whipple's disease[3,4]. Their value in the diagnosis of intestinal Whipple's disease has not been assessed.Figure 1. Endoscopic duodenal biopsy specimen showing flat mucosa (total villous atrophy), abundant large, pale-staining cells, and clear spaces of variable size within the lamina propria. (H&E;[A]×50; [B]×200, before reduction.)Download FigureFigure 2. Periodic acid-Schiff (PAS)-positive macrophages (darkly stained) in the lamina propria in a duodenal biopsy specimen exposed to diastase digestion. (H&E; [A]×50; [B]×200, before reduction.)Download FigureThe patient was initially treated with crystalline penicillin (1 megaunit 6 hourly for 11 days) and then penicillin V (500 mg 6 hourly for 5 days). Orally administered tetracycline (500 mg 6 hourly for 4 weeks) was started at the same time. Subsequently he was given trimethoprim-sulfa (two tablets twice daily) to be continued for one year.Within a week of starting antibiotic treatment there was dramatic clinical improvement, with complete cessation of diarrhea. His appetite improved greatly and he became ambulatory after two weeks' therapy. He was discharged home in satisfactory condition.Four weeks after discharge, the patient was readmitted with vomiting and diarrhea of 2 days' duration. This resolved with symptomatic treatment alone. However, during this admission he suffered an acute myocardial infarction with congestive cardiac failure, from which he recovered. Repeat endoscopy with biopsy done six weeks after starting antibiotics showed no significant improvement in the duodenal mucosa, endoscopically or histologically. At a recent review he was well and had gained weight. There has been marked improvement in his hematological and biochemical profile.DISCUSSIONWhipple's disease is a rare systemic disease that can affect many organs but presents predominantly with gastrointestinal symptoms. It was first described in 1907 by George Whipple, an American pathologist, who called it “intestinal lipodystrophy”[5]. Until 1988 only 741 cases had been reported worldwide[6]. It is thought to occur predominantly in Caucasians[1,2]. We believe that this is the first report of Whipple's disease in a Saudi national. A review of the Saudi Medical Bibliography from 1887 to 1986 revealed no reports of the disease[7]. A further search of Saudi medical publications up to June 1990 similarly failed to unearth any reports.Nearly 85% of the patients are male, with an average age of 50 years at the time of diagnosis. Clinical presentation varies but the main presenting features are malabsorption with diarrhea and weight loss, as was the case in our patient. Fever, skin pigmentation, anemia, generalized lymphadenopathy, arthritis, pleurisy, pericarditis, myocarditis, valvular endocarditis, glomerulonephritis, and central nervous system manifestations occur in some patients and may occasionally be the presenting features. The affected organ or tissue is infiltrated by large mononuclear phagocytes containing granular, diastase-resistant, PAS-positive material.The small intestine is invariably involved and diagnosis is usually made based on small intestinal biopsy findings. Barium studies are usually abnormal[8], the most characteristic feature being marked thickening of the mucosal folds, especially in the duodenum and proximal jejunum. Dilatation of the small bowel, as seen in our patient, is unusual but has been described. Endoscopy reveals thickened duodenal mucosal folds covered by miliary, yellowish, waxy nodules[9,10], as seen in our patient. The nodules may become confluent and even form plaques.Histologically there is broadening and stunting of the villi, and in severe cases, there may be subtotal or total villous atrophy resulting in a flat mucosa (see Figure 1). The most striking feature is the presence of numerous large foamy macrophages within the lamina propria. These contain abundant granular PAS-positive material, as previously noted. Small numbers of these cells may be seen in the submucosa. Small 1 to 2 μm bacillary organisms have been identified in the mucosa by electron microscopy[10–12] but these have not yet been cultured. They occur freely in the lamina propria as well as within the large foamy macrophages. They are believed to be the causative agent and they disappear after 4 to 8 weeks of antibiotic treatment[1]. The other histological finding in the intestinal mucosa is the presence of variably sized clear spaces that contain lipid (see Figure 1).[10]. PAS-positive mononuclear phagocytes also occur in the colonic mucosa and in other affected organs. The finding of these cells in the colonic mucosa alone cannot be used to diagnose Whipple's disease, as muciphages and macrophages containing lipofuscin have a similar appearance.Similar PAS-positive cells have been described in the intestinal mucosa of AIDS patients with Mycobacterium avium intracellulare infection[13,14]. They can be distinguished with acid-fast stains. An enzyme-linked immunosorbent assay for human immunodeficiency virus on the serum of our patient was negative and there were no acid-fast bacilli in the biopsies. The mesenteric lymph nodes may, in addition, show small non-caseating granulomas. The finding of PAS-positive macrophages in M. avium infections in AIDS patients, together with the finding of a helper T-cell deficiency[15], monocyte/macrophage abnormalities[16,17], and a lack of immunoglobulin-containing cells in the intestinal mucosa of some patients with Whipple's disease[18], have led to the suggestion that clinical Whipple's disease may result from an immunological deficit causing defective macrophage destruction of the engulfed causative bacteria.Whipple's disease bacilli have been identified in the walls of blood vessels in various organs and may be associated with vasculitis and intimai hyperplasia[19–21]. Our patient's myocardial infarction was presumably a consequence of his Whipple's disease and may have resulted from coronary arteritis with thrombosis.Most of the biochemical and hematological abnormalities found in Whipple's disease are related to severe intestinal malabsorption. Depending on the severity, there may be steatorrhea, hypocalcemia, hypomagnesemia, hypoalbuminemia, and anemia due to deficiencies of various nutritional factors.Whipple's disease is a curable condition, but all patients will die if it is not detected and treated effectively. Treatment with antibiotics produces a prompt and dramatic relief of symptoms in most patients. The morphological changes, however, take much longer to abate. Various antibiotics have been shown to be effective, but must be given for a long time otherwise there may be relapse. There are no controlled trials to show which antibiotic is the best and for how long it must be given. However, because brain involvement is life-threatening, the choice should include drugs that cross the blood–brain barrier. In a recently published retrospective study of 88 patients, Keinath et al[22] found that the use of a single antibiotic was associated with a higher relapse rate than the use of two or three. They recommend that penicillin and streptomycin be given for two weeks followed by trimethoprim-sulfa for one year. Relapses should be treated like new cases, and except for patients with central nervous system involvement, patients respond well.ARTICLE REFERENCES:1. Dobbins WO. Whipple's disease. Springfield, III: Thomas, 1987. Google Scholar2. Comer GM, Brandt LJ, Abissi CJ. "Whipple's disease: a review" . Am J Gastroenterol. 1983; 78: 107–14. Google Scholar3. Wietholter H, Dichgans J. "Diagnosis of cerebral Whipple's disease by cerebrospinal fluid cytology" . Arch Psy-chiatr Nervenkr. 1982; 231 (3): 283–7. Google Scholar4. Leger JM, Sauron B, Rousseau P, Gray F. "Whipple's disease with encephalopathy: a case report with review of the literature" . Rev Neurol (Paris). 1983; 139 (5): 375–9. Google Scholar5. Whipple GH. "A hitherto undescribed disease characterized anatomically by deposits of fat and fatty acids in the intestinal and mesenteric lymphatic tissues" . Bull Johns Hopkins Hosp. 1907; 19: 382–91. Google Scholar6. Dobbins WO. "Whipple's disease" . Mayo Clin Proc. 1988; 63: 623–4. Google Scholar7. Madkour MM, Kudwah AJ. Saudi Medical Bibliography, 1887-1980; 1981-82; 1983-84; 1986. Edinburgh: Churchill Livingstone, 1983, 1986. Google Scholar8. Philips RL, Carlson HC. "The roentgenographic and clinical findings in Whipple's disease" . Am J Roentgenol Rad Ther Nucl Med. 1975; 123: 269. Google Scholar9. Reiman JF, Rosch W. "Synopsis of endoscopie and related morphological findings in Whipple's disease" . Endoscopy. 1978; 10: 98. Google Scholar10. Morson BC, Dawson IMP, Day DW, et al.Morson & Dawson's gastrointestinal pathology, ed 3. Oxford: Blackwell, 1990;257–8. Google Scholar11. Dobbins WO, Kawanishi H. "Bacillary characteristics in Whipple's disease: an electron microscopic study" . Gastroenterology. 1981; 80: 1469. Google Scholar12. Silva MT, Macedo PM, Nunes JF. "Ultrastructure of bacilli and the bacillary origin of the macrophage inclusions in Whipple's disease" . J Gen Microbiol. 1985; 131 (Pt. 5): 1001–13. Google Scholar13. Billen JS, Urmacher C, West R, Shike M. "Disseminated Mycobacterium avium intracellulare infection in acquired immune deficiency syndrome mimicking Whipple's disease" . Gastroenterology. 1983; 85 (5): 1187–91. Google Scholar14. Roth RI, Owen RL, Keren DF, Velberding PA. "Intestinal infection with Mycobacterium avium in acquired immune deficiency syndrome (AIDS). Histologic and clinical comparison with Whipple's disease" . Dig Dis Sci. 1985; 30 (5): 497–504. Google Scholar15. Gras C, Kaplanski S, Farnarier C, et al. "Immunological profile of Whipple's disease evolving over a period of 17 years" . Ann Med Interne (Paris). 1988; 139 (l): 24–8. Google Scholar16. Bjerknes R, Laerum OD, Degaard S. "Impaired bacterial degradation by monocytes and macrophages from a patient with treated Whipple's disease" . Gastroenterology. 1985; 89 (5): 1139–46. Google Scholar17. Bjerknes R, Odegaard S, Bjerkvic R, et al. "Whipple's disease: demonstration of a persisting monocyte and macrophage dysfunction" . Scand J Gastroenterol. 1988; 23 (5): 611–9. Google Scholar18. Stoinov SG, Nikolov NP, Todonov DM, et al. "Whipple disease: clinical and immunohistologic findings in 2 cases" . Dtsch Z Verdau Stoffwechselkr. 1984; 44 (5): 232–40. Google Scholar19. James TN, Bulkley BH. "Abnormalities of the coronary arteries in Whipple's disease" . Am Heart J. 1983; 105 (3): 481–91. Google Scholar20. James TN, Bulkley BH. "Vascular lesions of the gastrointestinal system in Whipple's disease" . Am J Med Sci. 1984; 288 (3): 125–9. Google Scholar21. James TN, Bulkley BH. "Whipple bacilli within the tunica media of pulmonary arteries" . Chest. 1984; 86 (3): 454–8. Google Scholar22. Keinath RD, Merrel DE, Vlietstra R, et al. "Antibiotic treatment and relapse in Whipple's disease: long-term follow-up of 88 patients" . Gastroenterology. 1985; 88 (6): 1867–73. Google Scholar Previous article Next article FiguresReferencesRelatedDetails Volume 11, Issue 3May 1991 Metrics History Accepted30 July 1990Published online1 May 1991 ACKNOWLEDGMENTWe thank Dr. Ionel Bucur, consultant haematologist, and Mrs. Cleo Erwin, Librarian, King Fahad Hospital, Al-Baha; Miss Betty P. Lange, Senior Editor, Annals of Saudi Medicine; and Dr. M. B. Satti, Associate Professor of Pathology, King Faisal University, Dammam, for assisting us with the literature search.InformationCopyright © 1991, Annals of Saudi MedicinePDF download
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